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TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus.
Am J Physiol Gastrointest Liver Physiol. 2009 Jul; 297(1):G34-42.AJ

Abstract

Sensitization of esophageal sensory afferents by inflammatory mediators plays an important role in esophageal nociception. We have shown esophageal mast cell activation induces long-lasting mechanical hypersensitivity in vagal nodose C-fibers. However, the roles of mast cell mediators and downstream ion channels in this process are unclear. Mast cell tryptase via protease-activated receptor 2 (PAR2)-mediated pathways sensitizes sensory nerves and induces hyperalgesia. Transient receptor potential A1 (TRPA1) plays an important role in mechanosensory transduction and nociception. Here we tested the hypothesis that mast cell activation via a PAR2-dependent mechanism sensitizes TRPA1 to induce mechanical hypersensitivity in esophageal vagal C-fibers. The expression profiles of PAR2 and TRPA1 in vagal nodose ganglia were determined by immunostaining, Western blot, and RT-PCR. Extracellular recordings from esophageal nodose neurons were performed in ex vivo guinea pig esophageal-vagal preparations. Action potentials evoked by esophageal distention and chemical perfusion were compared. Both PAR2 and TRPA1 expressions were identified in vagal nodose neurons by immunostaining, Western blot, and RT-PCR. Ninety-one percent of TRPA1-positive neurons were of small and medium diameters, and 80% coexpressed PAR2. Esophageal mast cell activation significantly enhanced the response of nodose C-fibers to esophageal distension (mechanical hypersensitivity). This was mimicked by PAR2-activating peptide, which sustained for 90 min after wash, but not by PAR2 reverse peptide. TRPA1 inhibitor HC-030031 pretreatment significantly inhibited mechanical hypersensitivity induced by either mast cell activation or PAR2 agonist. Collectively, our data provide new evidence that sensitizing TRPA1 via a PAR2-dependent mechanism plays an important role in mast cell activation-induced mechanical hypersensitivity of vagal nodose C-fibers in guinea pig esophagus.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, The Milton S. Hershey Medical Center, Penn State University College of Medicine, 500 Univ. Drive, Hershey, PA 17033, USA. suy13@psu.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19423751

Citation

Yu, Shaoyong, et al. "TRPA1 in Mast Cell Activation-induced Long-lasting Mechanical Hypersensitivity of Vagal Afferent C-fibers in Guinea Pig Esophagus." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 297, no. 1, 2009, pp. G34-42.
Yu S, Gao G, Peterson BZ, et al. TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus. Am J Physiol Gastrointest Liver Physiol. 2009;297(1):G34-42.
Yu, S., Gao, G., Peterson, B. Z., & Ouyang, A. (2009). TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus. American Journal of Physiology. Gastrointestinal and Liver Physiology, 297(1), G34-42. https://doi.org/10.1152/ajpgi.00068.2009
Yu S, et al. TRPA1 in Mast Cell Activation-induced Long-lasting Mechanical Hypersensitivity of Vagal Afferent C-fibers in Guinea Pig Esophagus. Am J Physiol Gastrointest Liver Physiol. 2009;297(1):G34-42. PubMed PMID: 19423751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus. AU - Yu,Shaoyong, AU - Gao,Guofeng, AU - Peterson,Blaise Z, AU - Ouyang,Ann, Y1 - 2009/05/07/ PY - 2009/5/9/entrez PY - 2009/5/9/pubmed PY - 2009/8/6/medline SP - G34 EP - 42 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 297 IS - 1 N2 - Sensitization of esophageal sensory afferents by inflammatory mediators plays an important role in esophageal nociception. We have shown esophageal mast cell activation induces long-lasting mechanical hypersensitivity in vagal nodose C-fibers. However, the roles of mast cell mediators and downstream ion channels in this process are unclear. Mast cell tryptase via protease-activated receptor 2 (PAR2)-mediated pathways sensitizes sensory nerves and induces hyperalgesia. Transient receptor potential A1 (TRPA1) plays an important role in mechanosensory transduction and nociception. Here we tested the hypothesis that mast cell activation via a PAR2-dependent mechanism sensitizes TRPA1 to induce mechanical hypersensitivity in esophageal vagal C-fibers. The expression profiles of PAR2 and TRPA1 in vagal nodose ganglia were determined by immunostaining, Western blot, and RT-PCR. Extracellular recordings from esophageal nodose neurons were performed in ex vivo guinea pig esophageal-vagal preparations. Action potentials evoked by esophageal distention and chemical perfusion were compared. Both PAR2 and TRPA1 expressions were identified in vagal nodose neurons by immunostaining, Western blot, and RT-PCR. Ninety-one percent of TRPA1-positive neurons were of small and medium diameters, and 80% coexpressed PAR2. Esophageal mast cell activation significantly enhanced the response of nodose C-fibers to esophageal distension (mechanical hypersensitivity). This was mimicked by PAR2-activating peptide, which sustained for 90 min after wash, but not by PAR2 reverse peptide. TRPA1 inhibitor HC-030031 pretreatment significantly inhibited mechanical hypersensitivity induced by either mast cell activation or PAR2 agonist. Collectively, our data provide new evidence that sensitizing TRPA1 via a PAR2-dependent mechanism plays an important role in mast cell activation-induced mechanical hypersensitivity of vagal nodose C-fibers in guinea pig esophagus. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/19423751/TRPA1_in_mast_cell_activation_induced_long_lasting_mechanical_hypersensitivity_of_vagal_afferent_C_fibers_in_guinea_pig_esophagus_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00068.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -